Genome-Wide Association Study of Hunner-type Interstitial Cystitis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18552
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: The University of Tokyo
• Principal Investigator: AKIYAMA Yoshiyuki 東京大学, 医学部附属病院, 講師 (20529135)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 全ゲノム関連解析 / ハンナ型間質性膀胱炎 / HLA imputation / GWAS

Outline of Final Research Achievements

To examine the roles of human leukocyte antigen (HLA), which has been known to be associated with the risk of various autoimmune diseases, for Hunner-type interstitial cystitis (HIC) pathogenesis in Japanese, we fine-mapped HLA in 1,044 individuals (148 patients with HIC and 896 controls) We identified that one of the class Ⅱ HLA alleles of HLA-DQB1 was significantly associated with HIC risk. The conditional analysis demonstrated that no other HLA alleles remained significant after conditioning on the HLA-DQB1, suggesting that HLA-DQB1 could explain most of the MHC risk associated with HIC risk. The HLA amino acid residue-based analysis suggested that the amino acid position 75 of HLA-DQB1 plays a key role in the susceptibility to HIC (presence of valine being a risk, P = 1.4 × 10-6)

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、世界中で精力的に病態解明研究が行われているにも関わらず未だ病因不明の難病であるハンナ型間質性膀胱炎の発症に遺伝的要因が関与することを世界で初めて全ゲノム関連解析を施行して明らかにした。過去の研究から、HICは免疫学的異常を伴うことが示唆されていたが、本研究で特定された疾患感受性遺伝子領域は古典的ＭＨＣクラスⅡ領域のバリアントであり、非常に合理的な結果である。本研究結果からハンナ型間質性膀胱炎が免疫関連疾患であることはほぼ間違いなく、今後の治療法開発や病態解明の進歩に大きく寄与する点で学術的・社会的意義は大きい。現在、Nature関連雑誌への投稿を準備中である。